This proposal is designed to address the hypothesis that select components of cell-mediated immunity, specific for response to herpes simplex virus (HSV), are altered in patients undergoing primary HSV infection and progressing to subsequent recurrent disease. The components of cellular immunity to be examined are T cell subset recognition and proliferative response, and NK and K cell cytotoxic responses. For each cell system, the in vitro measurements of immunocompetence will be correlated to clinical disease progress and prognosis. It is postulated that: (1) patients who are subject to frequent or severe episodes of recurrent disease will express selective alterations of lymphocyte response to HSV, and (2) the immune cell components which participate to limit primary infection may be different from those which determine recurrence. Dependent on these findings from the initial phase of investigation, the cellular regulatory mechanisms responsible for the observed alterations in immune responsiveness to HSV will be explored. Although cell-mediated immunity is indicated as a decisive influence in limiting severity and duration of HSV infections in human disease, the involvement and relative importance of specific immune components remain to be elucidated. The goal of this project is to define the cellular immune parameters which contribute significantly to the host's ability to limit primary infection and susceptibility to recurrence. The identification of these components, and the exploration of the regulatory mechanisms controlling them, should contribute immensely toward the design of future approaches to the control and treatment of herpes infections.